基于静息态功能磁共振成像探讨耳甲电针治疗难治性抑郁症的即刻脑效应机制

Mechanism of immediate brain effect of transcutaneous auricular vagus nerve stimulation in treating treatment-resistant depression by rs-fMRI

目的:运用静息态功能磁共振成像技术(rs-fMRI),观察耳甲电针(ta V NS)治疗难治性抑郁症(TRD)的即刻脑效应。方法:纳入30例TRD患者及30例健康者,TRD组采用taVNS治疗30 min,并于治疗前后行rs-fMRI扫描,健康组仅纳入时行rs-fMRI扫描。分析基线期TRD组与健康组局部一致性(ReHo)有统计学差异的脑区,并以差异脑区为感兴趣区(ROI)分析TRD组即刻治疗前后的全脑功能连接(FC)变化。结果:与健康组比较,治疗前TRD组在左侧壳核/左侧杏仁核(t=4.36,P<0.005)、左侧直回/左侧前扣带回(t=4.77,P<0.005)升高,在右侧尾状核(t=-4.45,P<0.005)、左侧距状沟(t=-6.92,P<0.005)、左侧楔前叶/左侧中央旁小叶(t=-4.09,P<0.005)、右侧颞中回(t=-4.79,P<0.005)及左侧小脑蚓部2区(t=-5.54,P<0.005)减低。以右侧尾状核为ROI进行全脑FC分析,与健康组比较,治疗前TRD组在左侧楔前叶/右侧楔前叶(t=4.33,P<0.005)、左侧枕中回(t=3.66,P<0.005)的FC增强。与治疗前比较,治疗后TRD组左侧楔前叶/右侧楔前叶(t=-3.21,P<0.005)、左侧枕上回(t=-5.11,P<0.005)的FC减低。结论:TRD患者存在默认网络等脑区功能活动异常,且与“边缘系统-皮层-纹状体-苍白球-丘脑”神经解剖环路异常相关;taVNS具有调制尾状核-默认网络及视觉加工网络部分脑区功能活动的作用,这可能是其治疗TRD潜在的脑效应机制。

Objective:To observe the immediate brain effect of transcutaneous auricular vagus nerve stimulation(taVNS)on patients with treatment-resistant depression(TRD)by using rs-f MRI.Methods:Thirty TRD patients and 30 healthy individuals were included.The TRD group was treated with taVNS for 30 min and underwent rs-f MRI scans before and after treatment,and the healthy group underwent rs-fMRI scans at inclusion only.Brain areas with statistically significant differences in regional homogeneity(ReHo)between the TRD group and the healthy group at baseline were analysed,and changes in whole brain functional connectivity(FC)in the TRD group immediately before and after treatment were analysed using the difference brain areas as regions of interest(ROI).Results:Compared to the healthy group,the pre-treatment TRD group had elevated levels in the left lateral shell nucleus/left amygdala(t=4.36,P<0.005),left rectus/left anterior cingulate gyrus(t=4.77,P<0.005),in the right caudate nucleus(t=-4.45,P<0.005),left talar gyrus(t=-6.92,P<0.005),left precuneus/left paracentral lobule(t=-4.09,P<0.005),right middle temporal gyrus(t=-4.79,P<0.005)and left cerebellar earthworm area 2(t=-5.54,P<0.005)were reduced.Whole brain FC analysis was performed using the right caudate nucleus as the area of interest,and compared to the healthy group,the pre-treatment TRD group showed a reduction in the left precuneus/right precuneus(t=4.33,P<0.005),and the left middle occipital gyrus(t=3.66,P<0.005)had enhanced FC.After treatment,FC was reduced in the left precuneus/right precuneus(t=-3.21,P<0.005)and left supraoccipital gyrus(t=-5.11,P<0.005)in the TRD group compared to before treatment.Conclusion:TRD patients have abnormal functional activity in brain areas such as the default network,which is associated with abnormalities in the‘limbic system-cortex-striatum-pallidum-thalamus’neuroanatomical circuit;taVNS has the effect of modulating the functional activity of some brain areas in the caudate nucleus-default network and visual processing network,which may be a potential brain effect mechanism for its treatment of TRD.